Davis Michael E, Motion J P Michael, Narmoneva Daria A, Takahashi Tomosaburo, Hakuno Daihiko, Kamm Roger D, Zhang Shuguang, Lee Richard T
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Circulation. 2005 Feb 1;111(4):442-50. doi: 10.1161/01.CIR.0000153847.47301.80.
Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization.
In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet-endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express alpha-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein-positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment.
These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.
促进移植细胞或内源性前体细胞的存活是一个重要目标。我们推测,一种促进血管生成的新方法是在心肌内创建可注射的微环境,以募集内皮细胞并促进其存活和组织化。
在本研究中,我们证明自组装肽可以注射,并且在心肌内很容易检测到由此产生的纳米纤维微环境。此外,通过异凝集素染色和检测内皮特异性蛋白血小板内皮细胞黏附分子-1,确定自组装肽纳米纤维微环境募集了表达内皮标志物的祖细胞。血管平滑肌细胞被募集到微环境中,并似乎形成功能性血管结构。在内皮细胞群体之后,表达α-肌节肌动蛋白和转录因子Nkx2.5的细胞浸润肽微环境。当将外源性供体绿色荧光蛋白阳性新生心肌细胞与自组装肽一起注射时,肽微环境中的移植心肌细胞存活,并且还增强了内源性细胞募集。
这些实验表明,自组装肽可以在心肌内创建纳米纤维微环境,并且这些微环境促进血管细胞募集。由于这些肽纳米纤维可以通过多种方式进行修饰,这种方法可能实现可注射的组织再生策略。